Renal Medullary COX2 in Blood Pressure Regulation

Summary

Principal Investigator: Chuan Ming Hao
Abstract: As opposed to other tissues, the kidney exhibits abundant constitutive expression of inducible cyclooxygenase-2 (COX2) (18). Within the kidney, the vast majority of COX2 resides in the stromal/interstitial cells, with some COX2 expressed in the cortex in epithelial cells on macula densa and its adjacent fragment of cortical thick ascending limb. Studies indicate cyclooxygenase inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), including newly developed COX2 selective inhibitors (celecoxib, rofecoxib), cause sodium retention and hypertension in certain subsets of patients (21, 63, 64), pointing to an important role of renal COX2 mediated prostaglandins in regulating salt absorption and systemic blood pressure. Animal studies show renal medullary COX2 is markedly induced by high salt diet (69), consistent with the role of renal medullary COX2 in maintaining body sodium homeostasis. The present proposal will examine the hypothesis that high salt induced renal medullary interstitial (stromal) COX2 plays an important role in regulating renal medullary blood flow, salt excretion and maintaining systemic blood pressure. Defining the role of COX2 in renal interstitial cells should provide valuable information in identifying target molecule(s) or receptor(s) of renal COX2 mediated PGs. The proposed studies will have three specific aims: Specific Aim I: To examine the mechanism underlying high salt diet induced COX2 expression. Specific Aim II: To examine the role of renal medullary interstitial cell COX2 in modulating sodium excretion and maintaining blood pressure following high salt loading. Specific Aim III: To define the down-stream target of activated renal medullary COX2 expression.
Funding Period: 2005-07-15 - 2010-06-30
more information: NIH RePORT

Top Publications

  1. pmc Sirt1 activation protects the mouse renal medulla from oxidative injury
    Wenjuan He
    Nephrology Division, Vanderbilt University Medical Center School of Medicine, Nashville, Tennessee 37232, USA
    J Clin Invest 120:1056-68. 2010
  2. pmc Renal function, bisphenol A, and alkylphenols: results from the National Health and Nutrition Examination Survey (NHANES 2003-2006)
    Li You
    Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
    Environ Health Perspect 119:527-33. 2011
  3. ncbi Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting duct
    Monica Carmosino
    Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Am J Physiol Renal Physiol 292:F351-60. 2007
  4. ncbi Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice
    R Rao
    Division of Nephrology, Medical Center North, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Diabetologia 50:452-60. 2007
  5. ncbi Expression of nestin in the podocytes of normal and diseased human kidneys
    Wei Su
    Division of Nephrology, Huashan Hospital, Institute of Nephrology, Fudan University, Shanghai, PR Chiina
    Am J Physiol Regul Integr Comp Physiol 292:R1761-7. 2007
  6. ncbi Physiological regulation of prostaglandins in the kidney
    Chuan Ming Hao
    Division of Nephrology, Department of Medicine, Vanderbilt University, and Veterans Affair Medical Center, Nashville, TN 37232, USA
    Annu Rev Physiol 70:357-77. 2008
  7. pmc Increased dietary NaCl induces renal medullary PGE2 production and natriuresis via the EP2 receptor
    Jian Chen
    Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Am J Physiol Renal Physiol 295:F818-25. 2008

Scientific Experts

  • Chuan Ming Hao
  • Qi Dai
  • Reena Rao
  • Li You
  • Wenjuan He
  • Jing Chen
  • Matthew D Breyer
  • Hong Fan
  • Linda S Davis
  • Jian Chen
  • Monica Carmosino
  • Wei Su
  • Xiangzhu Zhu
  • Jie Dong
  • Martha J Shrubsole
  • Yingying Wang
  • Raymond C Harris
  • Hai Chun Yang
  • Roy Zent
  • Ming Zhi Zhang
  • Agnes B Fogo
  • Ginger L Milne
  • Min Zhao
  • Richard L H├ębert
  • Jocelyn R H Howard
  • Richard M Breyer
  • Jason Morrow
  • Lan Xu
  • Shanyan Lin
  • Haichun Yang
  • Hong Xu
  • Ruixi Li
  • Susan Opalenik
  • Heddwen L Brooks
  • Qi Cai
  • Xiang Wang
  • Yong Gu
  • Lu Gao

Detail Information

Publications7

  1. pmc Sirt1 activation protects the mouse renal medulla from oxidative injury
    Wenjuan He
    Nephrology Division, Vanderbilt University Medical Center School of Medicine, Nashville, Tennessee 37232, USA
    J Clin Invest 120:1056-68. 2010
    ..We therefore suggest that Sirt1 provides a potential therapeutic target to minimize renal medullary cell damage following oxidative stress...
  2. pmc Renal function, bisphenol A, and alkylphenols: results from the National Health and Nutrition Examination Survey (NHANES 2003-2006)
    Li You
    Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
    Environ Health Perspect 119:527-33. 2011
    ..Urinary excretion of bisphenol A (BPA) and alkylphenols (APs) was used as a biomarker in most previous studies, but no study has investigated whether urinary excretion of these environmental phenols differed by renal function...
  3. ncbi Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting duct
    Monica Carmosino
    Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Am J Physiol Renal Physiol 292:F351-60. 2007
    ..These findings further suggest distinct regulation of renal transport function by AVP through V1a and V2 receptors in the cortex vs. the medulla...
  4. ncbi Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice
    R Rao
    Division of Nephrology, Medical Center North, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Diabetologia 50:452-60. 2007
    ..In the current study, the effect of a highly specific peptide inhibitor of glycogen synthase kinase 3 (GSK3) (L803-mts) on glucose metabolism and BP was examined in a high-fat (HF) fed mouse model of diabetes...
  5. ncbi Expression of nestin in the podocytes of normal and diseased human kidneys
    Wei Su
    Division of Nephrology, Huashan Hospital, Institute of Nephrology, Fudan University, Shanghai, PR Chiina
    Am J Physiol Regul Integr Comp Physiol 292:R1761-7. 2007
    ..These studies suggest that nestin may play an important role in maintaining normal podocyte function in the human kidney...
  6. ncbi Physiological regulation of prostaglandins in the kidney
    Chuan Ming Hao
    Division of Nephrology, Department of Medicine, Vanderbilt University, and Veterans Affair Medical Center, Nashville, TN 37232, USA
    Annu Rev Physiol 70:357-77. 2008
    ..COXs, prostanoid synthases, and prostanoid receptors should provide fruitful targets for intervention in the pharmacological treatment of renal disease...
  7. pmc Increased dietary NaCl induces renal medullary PGE2 production and natriuresis via the EP2 receptor
    Jian Chen
    Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Am J Physiol Renal Physiol 295:F818-25. 2008
    ..Renal medullary PGE(2) promotes renal sodium excretion via the EP2 receptor, thereby maintaining normotension in the setting of high salt intake...